CCR2 limits inflammatory functions of CD8 TRM cells that impair recognition memory during recovery from WNV encephalitis [scRNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1160878 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30663530_1.fastq.gz | Fastqsanger.gz | |||
| SRR30663530_2.fastq.gz | Fastqsanger.gz | |||
| SRR30663531_1.fastq.gz | Fastqsanger.gz | |||
| SRR30663531_2.fastq.gz | Fastqsanger.gz | |||
| SRR30663532_1.fastq.gz | Fastqsanger.gz |
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Project description:Central nervous system (CNS) resident memory CD8 T cells (TRM) that express IFN-γ have been shown to contribute to neurodegenerative processes, including synapse loss, causing memory impairment. Here, we show that CCR2 deficiency in CD8 TRM that persists within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly contributes to poor cognitive outcomes. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2+ versus CCR2- CD8 TRM during WNV recovery reveal that CCR2 expression significantly regulates hippocampal CD8 TRM phenotype and function, with increased expression of CD103, granzyme A and IFN-γ. Consistent with this, WNV-recovered Cd8acreCcr2fl/fl mice exhibit decreased recognition memory. Our findings highlight CCR2's role in regulating CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections.
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Project description:Central nervous system (CNS) resident memory CD8 T cells (TRM) that express IFN-? have been shown to contribute to neurodegenerative processes, including synapse loss, causing memory impairment. Here, we show that CCR2 deficiency in CD8 TRM that persists within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly contributes to poor cognitive outcomes. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2+ versus CCR2- CD8 TRM during WNV recovery reveal that CCR2 expression significantly regulates hippocampal CD8 TRM phenotype and function, with increased expression of CD103, granzyme A and IFN-?. Consistent with this, WNV-recovered Cd8acreCcr2fl/fl mice exhibit decreased recognition memory. Our findings highlight CCR2's role in regulating CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections.
2025-01-02 | GSE277155 | GEO
Project description:Central nervous system (CNS) resident memory CD8 T cells (TRM) that express IFN-? have been shown to contribute to neurodegenerative processes, including synapse loss, causing memory impairment. Here, we show that CCR2 deficiency in CD8 TRM that persists within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly contributes to poor cognitive outcomes. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2+ versus CCR2- CD8 TRM during WNV recovery reveal that CCR2 expression significantly regulates hippocampal CD8 TRM phenotype and function, with increased expression of CD103, granzyme A and IFN-?. Consistent with this, WNV-recovered Cd8acreCcr2fl/fl mice exhibit decreased recognition memory. Our findings highlight CCR2's role in regulating CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections.
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Project description:CCR2 limits inflammatory functions of CD8 TRM cells that impair recognition memory during recovery from WNV encephalitis
| PRJNA1160288 | ENA
Project description:CCR2 limits inflammatory functions of CD8 TRM cells that impair recognition memory during recovery from WNV encephalitis [RNA-seq]
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Project description:West Nile virus (WNV) is the most important cause of endemic encephalitis in the USA. Strikingly, only a small percentage of patients develop clinical disease and of these patients, approximately 1 out of 150 patients develops encephalitis. The basis for this great variability in disease outcome is unknown, but may be related to the innate immune response. Innate immune responses, critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors (PRR) such as RIG-I and MDA5. IPS-1 is a key adaptor in generating a PRR-dependent interferon response.. Here we show that IPS-1 deficiency in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In IPS-1-/- mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were multifunctional and were able to lyse peptide-pulsed target cells in vitro. However, virus-specific T cells in the infected IPS-1-/- brain exhibited lower functional avidity than those in C57BL/6 brains, possibly contributing to less efficient virus clearance. The presence of virus-specific memory T cells was also not protective. We also show that macrophages were increased in numbers in the IPS-1-/- brain. Both macrophages and microglia exhibited an activated phenotype. Microarray analyses showed the preferential upregulation of genes associated with leukocyte activation and inflammation. Together, these results demonstrate the critical role that hematopoietic cell expression of Type 1 interferon and other IPS-1-dependent molecules have in WNV clearance and in regulating the inflammatory response. We used 4 mice in each group. STI knockout mice developed lethath encephalitis after WNV infectin. WT mice which have mild disease after WNV were used as controls.
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Project description:Comparative analysis of FACS-sorted CCR2- and CCR2+ HSC in the steady state. CCR2+ HSC have fourfold higher proliferative rates than CCR2- HSC, are are biased towards the myeloid lineage and dominate the migratory HSC population. Comparison of pooled CCR2- and CCR2+ HSC (bone marrow from 20 mice pooled for each sample), three biological replicates each.
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Project description:Flaviviruses, particularly Japanese encephalitis virus (JEV) and West Nile virus (WNV), are important causes of virus-induced central nervous system (CNS) disease in humans. We used microarray analysis to identify cellular genes that are differentially regulated following infection of the brain with JEV (P3) or WNV (New York 99). Gene expression data for these flaviviruses was compared to that induced following infection of the brain with reovirus (Type 3 Dearing), an unrelated neurotropic virus. Although several studies have described gene expression changes following virus infection of the brain, this report is the first to directly compare large-scale gene expression data from different viruses. We found that a large number of genes were up-regulated in common to infections with all 3 viruses (fold change > 2, P < 0.001), including genes associated with interferon signaling, the immune system, inflammation and cell death/survival signaling. In addition, genes associated with glutamate signaling were down-regulated in common to infections with all 3 viruses (fold change > 2, P < 0.001). These genes may serve broad spectrum therapeutic targets for virus-induced CNS disease. A distinct set of genes were up-regulated following flavivirus-infection, but not following infection with reovirus. These genes were associated with tRNA charging and may serve as therapeutic targets for flavivirus-induce CNS disease. Gene expression in the brain following WNV or JEV infection. WNV- or JEV-infected (N=3) vs. mock-infected (N=3) mouse brain.
2014-01-03 | E-GEOD-53784 | biostudies-arrayexpress
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